Various aspects of human gamma interferon (IFN-gamma) production and action will be studied. We have described the enhancing effect of various phorbol esters on IFN-gamma production in cultures of human lymphocytes. The mechanism of this enhancing effect will be examined. Specifically, the structural requirements of phorbol esters and related compounds associated with this activity will be determined. We shall also attempt to determine whether the enhancing effect of the phorbol esters is due too a direct effect on the cells producing IFN-gamma (T lymphocytes?) or whether it involves indirect action via an accessory cell. It has been shown that simultaneous treatment of cells with IFN-gamma and IFN-alpha or IFN-beta in some instances may result in a mutually potentiating effect. We shall examine whether such mutual potentiation regularly occurs in different cell systems. The evaluation will be based on inhibition of virus multiplication as well as inhibition of cell growth after combined treatments with different interferon preparations. Various parameters of the potentiating action will be studied in order to elucidate its mechanism.